scholarly journals The p97-UBXD8 complex modulates ER-Mitochondria contact sites by modulating membrane lipid saturation and composition

2021 ◽  
Author(s):  
Rakesh Ganji ◽  
Joao A. Paulo ◽  
Yuecheng Xi ◽  
Ian Kline ◽  
Jiang Zhu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Composition ◽  
Unsaturated Fatty Acids ◽  
Lipid Synthesis ◽  
Membrane Lipid ◽  
Loss Of Function ◽  
Membrane Lipid Composition ◽  
Aaa Atpase ◽  
Contact Sites ◽  
Lipid Species

AbstractThe intimate association between the endoplasmic reticulum (ER) and mitochondrial membranes at ER-mitochondria contact sites serves as a platform for several critical cellular processes, in particular lipid synthesis. Enzymes involved in lipid biosynthesis are enriched at contacts and membrane lipid composition at contacts is distinct relative to surrounding membranes. How contacts are remodeled and the subsequent biological consequences of altered contacts such as perturbed lipid metabolism remains poorly understood. Here we show that the p97 AAA-ATPase and its ER-tethered ubiquitin-X domain adaptor 8 (UBXD8) regulate the prevalence of ER-mitochondria contacts. The p97-UBXD8 complex localizes to contacts and loss of this complex increases contacts in a manner that is dependent on p97 catalytic activity. Quantitative proteomics of purified contacts demonstrates alterations in proteins regulating lipid metabolism upon loss of UBXD8. Furthermore, lipidomics studies indicate significant changes in distinct lipid species in UBXD8 knockout cells. We show that loss of p97-UBXD8 results in perturbed contacts due to an increase in membrane lipid saturation via SREBP1 and the lipid desaturase SCD1. Aberrant contacts in p97-UBXD8 loss of function cells can be rescued by supplementation with unsaturated fatty acids or overexpression of SCD1. Perturbation of contacts and inherent lipid synthesis is emerging as a hallmark to a variety of human disorders such as neurodegeneration. Notably, we find that the SREBP1-SCD1 pathway is negatively impacted in the brains of mice with p97 mutations that cause neurodegeneration. Our results suggest that contacts are exquisitely sensitive to alterations to membrane lipid composition and saturation in a manner that is dependent on p97-UBXD8.

Relationship between body size, Na+-K+-ATPase activity, and membrane lipid composition in mammal and bird kidney

2005 ◽  
Vol 288 (1) ◽  
pp. R301-R310 ◽  
Author(s):  
Nigel Turner ◽  
Kurt L. Haga ◽  
A. J. Hulbert ◽  
Paul L. Else
Keyword(s):  
Body Size ◽  
Atpase Activity ◽  
Lipid Composition ◽  
Unsaturated Fatty Acids ◽  
Cholesterol Content ◽  
Membrane Lipid ◽  
Enzyme Concentration ◽  
Membrane Lipid Composition ◽  
Mass Scaling ◽  
Metabolic Intensity

We investigated the relationship between body size, Na+-K+-ATPase molecular activity, and membrane lipid composition in the kidney of five mammalian and eight avian species ranging from 30-g mice to 280-kg cattle and 13-g zebra finches to 35-kg emus, respectively. Na+-K+-ATPase activity was found to be higher in the smaller species of both groups. In small mammals, the higher Na+-K+-ATPase activity was primarily the result of an increase in the molecular activity (turnover rate) of individual enzymes, whereas in small birds the higher Na+-K+-ATPase activity was the result of an increased enzyme concentration. Phospholipids from both mammals and birds contained a relatively constant percentage of unsaturated fatty acids; however, phospholipids from the smaller species were generally more polyunsaturated, and a complementary significant allometric increase in monounsaturate content was observed in the larger species. In particular, the relative content of the highly polyunsaturated docosahexaenoic acid [22:6( n-3)] displayed the greatest variation with body mass, scaling with allometric exponents of −0.21 and −0.26 in the mammals and birds, respectively. This allometric variation in fatty acid composition was correlated with Na+-K+-ATPase molecular activity in mammals, whereas in birds molecular activity only correlated with membrane cholesterol content. These relationships are discussed with respect to the metabolic intensity of different-sized animals.

scholarly journals Effect of elevated temperature on membrane lipid saturation in Antarctic notothenioid fish

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4765 ◽  
Author(s):  
Vanita C. Malekar ◽  
James D. Morton ◽  
Richard N. Hider ◽  
Robert H. Cruickshank ◽  
Simon Hodge ◽  
...  
Keyword(s):  
Fatty Acids ◽  
New Zealand ◽  
Lipid Composition ◽  
Unsaturated Fatty Acids ◽  
Antarctic Fish ◽  
Membrane Lipid ◽  
Thermal Acclimation ◽  
Homeoviscous Adaptation ◽  
Antarctic Species ◽  
Membrane Lipid Composition

Homeoviscous adaptation (HVA) is a key cellular response by which fish protect their membranes against thermal stress. We investigated evolutionary HVA (long time scale) in Antarctic and non-Antarctic fish. Membrane lipid composition was determined for four Perciformes fish: two closely related Antarctic notothenioid species (Trematomus bernacchiiandPagothenia borchgrevinki); a diversified related notothenioid Antarctic icefish (Chionodraco hamatus); and a New Zealand species (Notolabrus celidotus). The membrane lipid compositions were consistent across the three Antarctic species and these were significantly different from that of the New Zealand species. Furthermore, acclimatory HVA (short time periods with seasonal changes) was investigated to determine whether stenothermal Antarctic fish, which evolved in the cold, stable environment of the Southern Ocean, have lost the acclimatory capacity to modulate their membrane saturation states, making them vulnerable to anthropogenic global warming. We compared liver membrane lipid composition in two closely related Antarctic fish species acclimated at 0 °C (control temperature), 4 °C for a period of 14 days inT. bernacchiiand 28 days forP. borchgrevinki,and 6 °C for 7 days in both species. Thermal acclimation at 4 °C did not result in changed membrane saturation states in either Antarctic species. Despite this, membrane functions were not compromised, as indicated by declining serum osmolality, implying positive compensation by enhanced hypo-osmoregulation. Increasing the temperature to 6 °C did not change the membrane lipids ofP. borchgrevinki.However, inT. bernacchii,thermal acclimation at 6 °C resulted in an increase of membrane saturated fatty acids and a decline in unsaturated fatty acids. This is the first study to show a homeoviscous response to higher temperatures in an Antarctic fish, although for only one of the two species examined.

scholarly journals Impaired fetal erythrocytes' filterability: relationship with cell size, membrane fluidity, and membrane lipid composition

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2148-2153 ◽  
Author(s):  
FC Colin ◽  
Y Gallois ◽  
D Rapin ◽  
A Meskar ◽  
JJ Chabaud ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Membrane Fluidity ◽  
Lipid Composition ◽  
Fluorescence Polarization ◽  
High Performance ◽  
Unsaturated Fatty Acids ◽  
Membrane Lipid ◽  
Gas Liquid Chromatography ◽  
Biophysical Parameters ◽  
Membrane Lipid Composition

Abstract The lipid composition of erythrocytes (red blood cells [RBCs]) plays a significant role in determining certain membrane biophysical properties. We have found that fetal RBCs showed a dramatically low filterability compared with adult RBCs and questioned whether this could be a consequence of their membrane lipid composition. We therefore studied fetal RBCs at two different gestational ages, neonatal RBCs and adult RBCs. Biophysical parameters were studied using two different techniques, filterability and membrane fluidity. The latter was measured by fluorescence polarization using three different probes. The membrane lipid composition was examined by measuring cholesterol and phospholipids. After extraction of the phospholipids, followed by high performance thin-layer chromatography, the fatty acids in the phospholipid subfractions were analyzed by gas-liquid chromatography. The fetal RBCs' filterability was found to be correlated with both the larger size and the higher hemoglobin content of the cells, but there was no correlation between RBC filterability and fluidity or membrane lipid composition. In adult RBCs, compared with neonatal RBCs, the slight increase of unsaturated fatty acids in phosphatidylcholine and phosphatidylethanolamine should have increased the membrane fluidity. However, in RBCs, no change was observed in the fluidity parameters measured by fluorescence polarization.

scholarly journals Impaired fetal erythrocytes' filterability: relationship with cell size, membrane fluidity, and membrane lipid composition

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2148-2153
Author(s):  
FC Colin ◽  
Y Gallois ◽  
D Rapin ◽  
A Meskar ◽  
JJ Chabaud ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Membrane Fluidity ◽  
Lipid Composition ◽  
Fluorescence Polarization ◽  
High Performance ◽  
Unsaturated Fatty Acids ◽  
Membrane Lipid ◽  
Gas Liquid Chromatography ◽  
Biophysical Parameters ◽  
Membrane Lipid Composition

The lipid composition of erythrocytes (red blood cells [RBCs]) plays a significant role in determining certain membrane biophysical properties. We have found that fetal RBCs showed a dramatically low filterability compared with adult RBCs and questioned whether this could be a consequence of their membrane lipid composition. We therefore studied fetal RBCs at two different gestational ages, neonatal RBCs and adult RBCs. Biophysical parameters were studied using two different techniques, filterability and membrane fluidity. The latter was measured by fluorescence polarization using three different probes. The membrane lipid composition was examined by measuring cholesterol and phospholipids. After extraction of the phospholipids, followed by high performance thin-layer chromatography, the fatty acids in the phospholipid subfractions were analyzed by gas-liquid chromatography. The fetal RBCs' filterability was found to be correlated with both the larger size and the higher hemoglobin content of the cells, but there was no correlation between RBC filterability and fluidity or membrane lipid composition. In adult RBCs, compared with neonatal RBCs, the slight increase of unsaturated fatty acids in phosphatidylcholine and phosphatidylethanolamine should have increased the membrane fluidity. However, in RBCs, no change was observed in the fluidity parameters measured by fluorescence polarization.

scholarly journals Beyond Proteostasis: Lipid Metabolism as a New Player in ER Homeostasis

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 52
Author(s):  
Jiaming Xu ◽  
Stefan Taubert
Keyword(s):  
Lipid Metabolism ◽  
Lipid Composition ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Membrane Lipid ◽  
Normal Function ◽  
Metabolic Disturbances ◽  
Membrane Lipid Composition ◽  
Custom Made ◽  
Er Homeostasis

Biological membranes are not only essential barriers that separate cellular and subcellular structures, but also perform other critical functions such as the initiation and propagation of intra- and intercellular signals. Each membrane-delineated organelle has a tightly regulated and custom-made membrane lipid composition that is critical for its normal function. The endoplasmic reticulum (ER) consists of a dynamic membrane network that is required for the synthesis and modification of proteins and lipids. The accumulation of unfolded proteins in the ER lumen activates an adaptive stress response known as the unfolded protein response (UPR-ER). Interestingly, recent findings show that lipid perturbation is also a direct activator of the UPR-ER, independent of protein misfolding. Here, we review proteostasis-independent UPR-ER activation in the genetically tractable model organism Caenorhabditis elegans. We review the current knowledge on the membrane lipid composition of the ER, its impact on organelle function and UPR-ER activation, and its potential role in human metabolic diseases. Further, we summarize the bi-directional interplay between lipid metabolism and the UPR-ER. We discuss recent progress identifying the different respective mechanisms by which disturbed proteostasis and lipid bilayer stress activate the UPR-ER. Finally, we consider how genetic and metabolic disturbances may disrupt ER homeostasis and activate the UPR and discuss how using -omics-type analyses will lead to more comprehensive insights into these processes.

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